The cover image is based on the Original Article Perineuronal nets are phagocytosed by MMP-9 expressing microglia and astrocytes in the SOD1G93A ALS mouse model by Sang Won Cheung et al., https://doi.org/10.1111/nan.12982.

The brainstems of diseased Ndufs4(−/−) mice—a mouse model of the genetic mitochondrial disease Leigh syndrome (LS)—have elevated levels of cytokines IP10 and IFNγ. To explore the role of these two factors in LS, we generated IFNγ and IP10 deficient Ndufs4(−/−) mice and evaluated survival and disease pathology. Loss of IP10 does not impact disease in Ndufs4(−/−) mice, but IFNγ loss prolongs survival and delays disease progression, indicating that IFNγ signaling contributes to disease onset and progression in LS.

Perineuronal nets (PNNs) surrounding motoneurons in ALS model mice are broken down by a process of MMP-9 release from and engulfment by microglia and astrocytes, during disease progression. (1) Activated microglia and astrocytes are recruited to motoneurons. (2) MMP-9 released by these microglia assist in the breakdown of PNNs around motoneurons and digest PNN fragments. (3) CX3CL1 released from motoneurons triggers microglia to phagocytose PNNs. (4) These motoneurons are then made vulnerable to stress as seen by the upregulation of 3-NT.

We assessed the effectiveness of nanopore long-read sequencing for evaluatingmethylation levels across the MGMT CpG-island, crucial for prognosis in glioblastomapatients. Using 165 CNS tumour samples, nanopore sequencing was compared toestablished techniques, showing a strong correlation with pyrosequencing and effectivepatient stratification via hierarchical clustering. Nanopore sequencing provided rapid,high-confidence results and expanded analysis to all 98 CpGs of the MGMT CpG-island,suggesting its utility for clinically relevant patient subgroup identification and warranting further exploration in clinical settings.

The role of the metalloproteinase ADAMTS4 in the generation of N-terminally elongated Aβ peptide species has been characterized with cell-free and cell-based assays in combination with mass spectrometry. Immunohistochemical analysis revealed the deposition of N-terminally elongated Ab variants in the brains of a subset of AD patients.

Radiation induced pyroptosis in microglia, promoting radiation-induced brain injury via the secretion of neurotoxic cytokines. NLRP3 was evaluated as an important mediator in radiation-induced pyroptosis and a promising therapeutic target of radiation-induced brain injury. The patients after irradiation with higher IL-6 were found to have a decreased MMSE score, indicating that the level of IL-6 could serve as a valuable biomarker for radiation-induced brain injury.

Polyglucosan storage disorders represent an emerging field within neurodegenerative and neuromuscular conditions. We combined molecular genetic analyses, quantitative mass spectrometry of laser micro-dissected polyglucosan bodies, immunohistochemistry and western blot, and show that the absence of glycogenin-1 (GYG1), a protein important for glycogen synthesis initiation, causes storage of polyglucosan that displays accumulation of several proteins, including those essential for glycogen synthesis, sequestosome 1/p62 and desmin.

In this case report, we describe a 46-year-old patient with a brain lesion identified with imaging studies following a minor head injury. Initially suspected to be diffuse glioma, detailed histological, immunohistochemical and molecular investigations revealed characteristics consistent with an atypical teratoid/rhabdoid tumour (AT/RT), SHH-1B molecular subtype.